Enzymatic conjugation of polypeptides
First Claim
1. A composition comprising a plurality of antibodies or antibody fragments, wherein the plurality of antibodies or antibody fragments share the same heavy and/or light chain amino acid sequence, and wherein at least 90% of the antibodies or antibody fragments in said composition have (m) functionalized acceptor glutamine residues (Q) per antibody or fragment, wherein m is an integer selected from 2 or 4, and wherein each of the functionalized acceptor glutamine residues has the structure of Formula IVc,
(Q)NHC-X-L-RR′
- -L′
-V-Y-Z
Formula IVcor a pharmaceutically acceptable salt or solvate thereof,wherein;
Q is a glutamine residue present within or appended to a constant region of the antibodies or antibody fragments;
C is a substituted alkyl chain, an unsubstituted alkyl chain, a substituted heteroalkyl chain, or an unsubstituted heteroalkyl chain;
X is NH, O, S, absent, or a bond;
L is independently absent, a bond or a continuation of a bond, or a carbon comprising framework of 1 to 200 atoms substituted at one or more atoms;
(RR′
) is an addition product between a reactive moiety R and a complementary reactive moiety R′
;
L′
is independently absent, a bond or a continuation of a bond, or a carbon comprising framework of 1 to 200 atoms substituted at one or more atoms;
V is independently absent, a bond or a continuation of a bond, a non-cleavable moiety or a conditionally-cleavable moiety;
Y is independently absent, a bond or a continuation of a bond, or a spacer system which is comprised of 1 or more spacers; and
Z is a pyrrolobenzodiazepine,wherein the antibodies or antibody fragments specifically bind to a tumor antigen.
2 Assignments
0 Petitions
Accused Products
Abstract
The present application relates to methods for the enzymatic functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.
91 Citations
21 Claims
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1. A composition comprising a plurality of antibodies or antibody fragments, wherein the plurality of antibodies or antibody fragments share the same heavy and/or light chain amino acid sequence, and wherein at least 90% of the antibodies or antibody fragments in said composition have (m) functionalized acceptor glutamine residues (Q) per antibody or fragment, wherein m is an integer selected from 2 or 4, and wherein each of the functionalized acceptor glutamine residues has the structure of Formula IVc,
(Q)NHC-X-L-RR′- -L′
-V-Y-Z
Formula IVcor a pharmaceutically acceptable salt or solvate thereof, wherein; Q is a glutamine residue present within or appended to a constant region of the antibodies or antibody fragments; C is a substituted alkyl chain, an unsubstituted alkyl chain, a substituted heteroalkyl chain, or an unsubstituted heteroalkyl chain; X is NH, O, S, absent, or a bond; L is independently absent, a bond or a continuation of a bond, or a carbon comprising framework of 1 to 200 atoms substituted at one or more atoms; (RR′
) is an addition product between a reactive moiety R and a complementary reactive moiety R′
;L′
is independently absent, a bond or a continuation of a bond, or a carbon comprising framework of 1 to 200 atoms substituted at one or more atoms;V is independently absent, a bond or a continuation of a bond, a non-cleavable moiety or a conditionally-cleavable moiety; Y is independently absent, a bond or a continuation of a bond, or a spacer system which is comprised of 1 or more spacers; and Z is a pyrrolobenzodiazepine, wherein the antibodies or antibody fragments specifically bind to a tumor antigen. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
- -L′
-
21. A composition comprising a plurality of antibodies or antibody fragments wherein the plurality of antibodies or antibody fragments share the same heavy and/or light chain amino acid sequence, and wherein at least 90% of the antibodies or antibody fragments in said composition have (m) functionalized acceptor glutamine residues (Q) per antibody or fragment, wherein m is an integer selected from 2 or 4, wherein each of the functionalized acceptor glutamine residues has the structure:
-
(Q)-L″
-RR′
-Y-Zor a pharmaceutically acceptable salt or solvate thereof, wherein; Q is a glutamine residue present within or appended to a constant region of the antibodies or antibody fragments; L″
is a lysine-based linker in which the nitrogen atom is covalently bonded to the y carbon of Q as a secondary amine;(RR′
) is an addition product between a reactive moiety R and a complementary reactive moiety R′
;Y is a spacer system; and Z is a pyrrolobenzodiazepine, wherein the antibodies or antibody fragments specifically bind to a tumor antigen.
-
Specification